Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors

T M M Raposo-Ferreira1, R C Bueno2, E M Terra1

  • 1Department of Veterinary Clinic and Surgery, UNESP, Jaboticabal, São Paulo, Brazil.

Veterinary Pathology
|April 24, 2016
PubMed

Insights

Ataxia telangiectasia mutated (ATM) gene and protein are downregulated in canine mammary tumors. This suggests ATM

Area of Science:

  • Veterinary Oncology
  • Molecular Biology
  • Genetics

Background:

  • The ataxia telangiectasia mutated (ATM) gene is crucial for DNA repair and genomic stability.
  • ATM downregulation and absence of its protein expression are linked to poor prognosis in human breast cancer.
  • ATM's role in canine mammary tumors remains largely unexplored.

Purpose of the Study:

  • To investigate ATM gene and protein expression in canine mammary tumors.
  • To determine the association between ATM expression and clinical outcomes in dogs with mammary tumors.

Main Methods:

  • Quantitative analysis of ATM gene expression using reverse transcription-quantitative polymerase chain reaction.
  • Immunohistochemistry to evaluate ATM protein expression.
  • Comparison of ATM levels in normal mammary glands, benign tumors, and nonmetastatic/metastatic carcinomas.

Main Results:

  • Lower ATM transcript levels were observed in benign mammary tumors and carcinomas compared to normal mammary glands.
  • ATM protein expression was significantly reduced in benign tumors and all grades of mammary carcinomas versus normal tissue.
  • No significant differences in ATM gene or protein levels were found among benign, nonmetastatic, and metastatic mammary carcinomas.
  • ATM expression levels did not correlate with clinical-pathological features or survival outcomes.

Conclusions:

  • ATM gene and protein downregulation occurs during canine mammary gland tumorigenesis.
  • Similar to human breast cancer, ATM alterations are implicated in the development of canine mammary tumors.
  • Further research is needed to understand the precise role of ATM in canine mammary tumor progression and prognosis.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.3K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.2K